title: Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors.
abstract: A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3'OH and block intasome activity.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Yu
authors.forename: Tino Wilson
authors.initials: TW
authors.lastname: Sanchez
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Yin
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.forename: Guisen
authors.initials: G
authors.lastname: Zhao
mesh_terms: D020134:Catalytic Domain; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D011744:Pyrimidinones
keywords: HIV-1; Integrase inhibitors; Pyrimidone analogues